Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anorexia and weight loss are common findings in older persons. Over a life-time, normal persons decrease their food intake to counterbalance the decrease in physical activity and resting metabolic rate that occurs with aging. This physiological anorexia of aging increases the propensity to develop pathological anorexia and weight loss when an older person develops either a medical or psychological illness. The physiological anorexia of aging is due to a decreased opioid (dynorphin) feeding drive and an increase in the satiating effect of the gastrointestinal hormone, cholecystokinin. Nitric oxide deficiency may play a role in the early satiation commonly seen in older persons. A variety of social, psychological and medical conditions can lead to pathological anorexia. Depression is the most common cause of weight loss and anorexia in older persons. A number of conditions such as cancer and rheumatoid arthritis produce their anorectic and wasting effects by releasing cytokines. An idiopathic pathological senile anorexia has been characterised which also appears to be a cytokine-dependent syndrome. Early screening for malnutrition is a cornerstone of the management of anorexia; the Mini Nutritional Assessment is a well validated screening tool available for this purpose. Aggressive use of caloric supplements, enteral tube feeding and peripheral parenteral nutrition all have a role in the early management of anorexia. Numerous drugs (growth hormone, megestrol, cyproheptadine, tetrahydrocannabinol, anabolic steroids, prokinetic agents and antidepressants) have been utilised to treat the anorexia of aging with varying success.
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PMID:Anorexia in older persons: epidemiology and optimal treatment. 884 87

Six Welsh gelding ponies (weight 246 +/- 6 kg) were premedicated with 0.03 mg/kg of acepromazine intravenously (i.v.) followed by 0.02 mg/kg of detomidine i.v. Anaesthesia was induced with 2 mg/kg of ketamine i.v. Ponies were intubated and lay in left lateral recumbency. On one occasion anaesthesia was maintained for 2 h using 1.2% halothane in oxygen. The same group of ponies were anaesthetized 1 month later using the same induction regime and anaesthesia was maintained with a combination of detomidine, ketamine and guaiphenesin, while the ponies breathed oxygen-enriched air. Electrocardiogram, heart rate, mean arterial blood pressure, cardiac output, respiratory rate, blood gases, temperature, haematocrit, glucose, lactate and cortisol were measured and cardiac index and systemic vascular resistance were calculated in both groups. Beta-endorphin, met-enkephalin, dynorphin, arginine vasopressin (AVP), adrenocorticotrophic hormone (ACTH) and catecholamines were measured in the halothane anaesthesia group only and 11-deoxycortisol during total intravenous anaesthesia (TIVA) only. Cardiorespiratory depression was more marked during halothane anaesthesia. Hyperglycaemia developed in both groups. Lactate and AVP increased during halothane anaesthesia. Cortisol increased during halothane and decreased during TIVA. There were no changes in the other hormones during anaesthesia. Recovery was smooth in both groups. TIVA produced better cardiorespiratory performance and suppressed the endocrine stress response observed during halothane anaesthesia.
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PMID:Cardiorespiratory, endocrine and metabolic changes in ponies undergoing intravenous or inhalation anaesthesia. 886 52

1. Single pulse electrical field stimulation (EFS, 0.5 ms pulse width, 60 V at a frequency of 0.05 Hz) induced twitch contractions of mucosa-free circular muscle strips from the guinea-pig proximal colon which were abolished by atropine (0.3 microM), tetrodotoxin (0.3 microM) or omega-conotoxin GVIA (0.1 microM). 2. Various opioid receptor agonist concentration-dependently inhibited twitches with the following rank order of potency (EC50 values in brackets): U 50488 (0.31 nM) > dermorphin (4.3 nM) = dynorphin A (1-13) (6.2 nM) > [D-Ala2, N-MePhe4, Gly5-ol]-enkephalin (DAMGO, 33.5 nM) = [D-Ala2, D-Leu5]-enkephalin (DADLE, 60 nM) > [D-Pen2, D-Pen2, D-Pen5]-enkepahlin (DPDPE, 1144 nM). 3. Peptidase inhibitors (captopril, thiorphan and bestatin, 1 microM each) did not modify the amplitude of twitches. In the presence of peptidase inhibitors the concentration-response curve to dynorphin A (1-13) was displaced to the left to yield an EC50 of 0.35 nM, comparable to that of the selective kappa receptor agonist, U50488. The curves to the other opioid receptor agonist were unaffected by peptidase inhibitors. 4. DPDPE, DADLE, dermorphin and DAMGO consistently induced a concentration-unrelated transient increase in basal tone and a small and transient facilitation of twitches before development of their inhibitory effect. These transient excitatory effects were not observed upon application of dynorphin A (1-13) or U 50488. The contraction produced by DPDPE (30 nM) was largely inhibited (> 80%) by 1 microM atropine. 5. Twitches suppression induced by dynorphin A (1-13) (30 nM) was partly reversed (46 +/- 8%, n = 6) by naloxone (0.3 microM). The potent and selective kappa opioid receptor antagonist nor-binaltorphimine (Nor-BNI, 3-100 nM)) did not affect the amplitude of twitches and potently antagonized (pKB 9.83 +/- 0.09, n = 10) the inhibitory effect of dynorphin. 6. Naloxone (1-300 nM) concentration-dependently depressed the cholinergic twitches: this depressant effect was largely counteracted in the presence of apamin (0.1 microM) and NG-nitro-L-arginine (30 microM) which potentiated cholinergic twitches on their own. 7. Dynorphin A (1-13) (10 nM, n = 6) did not affect the contractile response to exogenous acetylcholine (1 microM), indicating that depression of evoked twitches occurs prejunctionally. 8. We conclude that multiple opioid receptors modulate cholinergic twitches in the circular muscle of guinea-pig proximal colon. While mu and delta opioid receptor agonists produced mixed excitatory and inhibitory effects, kappa opioid receptors, activated by sub-nanomolar concentrations of dynorphin A (1-13), mediate a powerful and pure prejunctional inhibition of acetylcholine release.
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PMID:Role of kappa opioid receptors in modulating cholinergic twitches in the circular muscle of guinea-pig colon. 892 49

Six Welsh gelding ponies were premedicated with 0.03 mg/kg of acepromazine intravenously (i.v.) prior to induction of anaesthesia with midazolam at 0.2 mg/kg and ketamine at 2 mg/kg i.v.. Anaesthesia was maintained for 2 h using 1.2% halothane concentration in oxygen. Heart rate, electrocardiograph (ECG), arterial blood pressure, respiratory rate, blood gases, temperature, haematocrit, plasma arginine vasopressin (AVP), dynorphin, beta-endorphin, adrenocorticotropic hormone (ACTH), cortisol, dopamine, noradrenaline, adrenaline, glucose and lactate concentrations were measured before and after premedication, immediately after induction, every 20 min during anaesthesia, and at 20 and 120 min after disconnection. Induction was rapid, excitement-free and good muscle relaxation was observed. There were no changes in heart and respiratory rates. Decrease in temperature, hyperoxia and respiratory acidosis developed during anaesthesia and slight hypotension was observed (minimum value 76 +/- 10 mm Hg at 40 mins). No changes were observed in dynorphin, beta-endorphin, ACTH, catecholamines and glucose. Plasma cortisol concentration increased from 220 +/- 17 basal to 354 +/- 22 nmol/L at 120 min during anaesthesia; plasma AVP concentration increased from 3 +/- 1 basal to 346 +/- 64 pmol/L at 100 min during anaesthesia and plasma lactate concentration increased from 1.22 +/- 0.08 basal to 1.76 +/- 0.13 mmol/L at 80 min during anaesthesia. Recovery was rapid and uneventful with ponies taking 46 +/- 6 min to stand. When midazolam/ketamine was compared with thiopentone or detomidine/ketamine for induction before halothane anaesthesia using an otherwise similar protocol in the same ponies, it caused slightly more respiratory depression, but less hypotension. Additionally, midazolam reduced the hormonal stress response commonly observed during halothane anaesthesia and appears to have a good potential for use in horses.
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PMID:Midazolam and ketamine induction before halothane anaesthesia in ponies: cardiorespiratory, endocrine and metabolic changes. 913 43

Effects of enkephalin and selective opioid-receptor agonists on GABA-induced current were examined in dissociated neurons of bullfrog dorsal root ganglia (DRG) by using whole-cell patch-clamp method. Leucine- (Leu)-enkephalin and methionine- (Met)-enkephalin depressed GABA(A) receptor-mediated currents. DPDPE, DAMGO and dynorphin-A (Dyn-A) also depressed the inward current produced by GABA; the order of agonist potency was DPDPE > DAMGO > Dyn-A. Naloxone blocked the inhibitory effects of enkephalins and other opioid agonists on the GABA current. Naltrindole (NTI), a delta-receptor antagonist, prevented the DPDPE-induced depression of the GABA current. beta-Funaltrexamine (beta-FNA), a mu-receptor antagonist, reduced the DAMGO-induced depression of GABA currents. Nor-binaltorphimine (nor-BNI), a kappa-receptor antagonist, reduced the effects of Dyn-A in depressing the GABA current. The results suggest that enkephalin down-regulates GABA(A) receptor function through mainly delta- and mu-opioid receptors in bullfrog DRG neurons.
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PMID:Opioid peptides modulate GABA(A) receptor responses in neurons of bullfrog dorsal root ganglia. 920 45

Despite the increase in body fat and obesity that occurs with aging, there is a linear decrease in food intake over the life span. This conundrum is explained by decreased physical activity and altered metabolism with aging. Thus, older persons fail to adequately regulate food intake and develop a physiologic anorexia of aging. This physiologic anorexia depends not only on decreased hedonic qualities of feeding with aging (an area that remains controversial) but also on altered hormonal and neurotransmitter regulation of food intake. Findings in older animals and humans have provided clues to the causes of the anorexia of aging. An increase in circulating concentrations of the satiating hormone, cholecystokinin, occurs with aging in humans. In addition, animal studies suggest a decrease in the opioid (dynorphin) feeding drive and possibly in neuropeptide Y and nitric oxide. The physiologic anorexia of aging puts older persons at high risk for developing protein-energy malnutrition when they develop either psychologic or physical disease processes. Despite its high prevalence, however, protein-energy malnutrition in older persons is rarely recognized and even more rarely treated appropriately. Screening tools for the early detection of protein-energy malnutrition in older persons have been developed. Multiple treatable causes of pathologic anorexia have been identified. There is increasing awareness of the importance of depression as a cause of severe weight loss in older persons. Approaches to the management of anorexia and weight loss in older persons are reviewed. Although many drugs exist that can enhance appetite, none of these are ideal for use in older persons currently.
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PMID:Anorexia of aging: physiologic and pathologic. 973 60

Experimental and clinical studies suggest an involvement of the opioid neuropeptide system in psychiatric disorders. Notably, opioid peptide immunoreactivity is altered in the cerebrospinal fluid of chronic schizophrenics and manic-depressive subjects. Despite these clinical findings, few postmortem investigations have examined the association of endogenous opioid neuropeptides with schizophrenia and suicide. Anatomically, a tight interaction exists within the neostriatum between the opioid peptide (dynorphin and enkephalin) system and classical neurotransmitters such as dopamine which has been implicated in both the psychotic symptoms and the cognitive deficits that characterize schizophrenia (see review). The neostriatum is differentially organized into patch and matrix neurochemical mosaic compartments anatomically connected to limbic- and sensorimotor-related brain regions, respectively. Moreover, the human neostriatum is characterized by a heterogenous expression of the prodynorphin opioid gene: high in the patch, but low in the matrix compartment. The present results show for the first time a differential alteration of prodynorphin within distinct striatal compartments in postmortem tissue from nonschizophrenic suicide subjects. The prodynorphin patch/matrix mRNA expression was elevated in the caudate nucleus of suicide subjects as compared to normal controls and schizophrenics in which no alterations in opioid peptides or D1 and D2 mRNA expression were apparent. Altogether the findings suggest that discrete dysfunction of the endogenous opioid dynorphin system might contribute to depression and the risk of suicide in nonschizophrenic subjects.
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PMID:Prodynorphin mRNA expression is increased in the patch vs matrix compartment of the caudate nucleus in suicide subjects. 939 95

Acute exposure to high doses of toluene can generate respiratory depression. However, neurotoxic mechanism of its action in the brainstem is not completely clear. In this work, acute, but not subchronic, exposure of rats to toluene increased leu-enkephalin immunostaining in several myelencephalic nuclei implicated in cardiorespiratory control. Due to the physiological role of enkephalins in the central regulation of breathing, it is suggested that the enkephalinergic system could play a role in neurotoxic respiratory depression induced by high dose acute toluene exposure.
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PMID:Toluene alters brainstem enkephalinergic system in rats. 970 3

The endogenous kappa receptor selective opioid peptide dynorphin has been shown to inhibit glutamate receptor-mediated neurotransmission and voltage-dependent Ca2+ channels. It is thought that dynorphin can be released from hippocampal dentate granule cells in an activity-dependent manner. Since actions of dynorphin may be important in limiting excitability in human epilepsy, we have investigated its effects on voltage-dependent Ca2+ channels in dentate granule cells isolated from hippocampi removed during epilepsy surgery. One group of patients showed classical Ammon's horn sclerosis characterized by segmental neuronal cell loss and astrogliosis. Prominent dynorphin-immunoreactive axon terminals were present in the inner molecular layer of the dentate gyrus, indicating pronounced recurrent mossy fiber sprouting. A second group displayed lesions in the temporal lobe that did not involve the hippocampus proper. All except one of these specimens showed a normal pattern of dynorphin immunoreactivity confined to dentate granule cell somata and their mossy fiber terminals in the hilus and CA3 region. In patients without mossy fiber sprouting the application of the kappa receptor selective opioid agonist dynorphin A ([D-Arg6]1-13, 1 microM) caused a reversible and dose-dependent depression of voltage-dependent Ca2+ channels in most granule cells. These effects could be antagonized by the non-selective opioid antagonist naloxone (1 microM). In contrast, significantly less dentate granule cells displayed inhibition of Ca2+ channels by dynorphin A in patients with mossy fiber sprouting (Chi-square test, P < 0.0005). The lack of dynorphin A effects in patients showing mossy fiber sprouting compares well to the loss of kappa receptors on granule cells in Ammon's horn sclerosis but not lesion-associated epilepsy. Our data suggest that a protective mechanism exerted by dynorphin release and activation of kappa receptors may be lost in hippocampi with recurrent mossy fiber sprouting.
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PMID:Loss of dynorphin-mediated inhibition of voltage-dependent Ca2+ currents in hippocampal granule cells isolated from epilepsy patients is associated with mossy fiber sprouting. 1057 9

Drugs of abuse regulate the transcription factor cAMP response element-binding protein (CREB) in striatal regions, including the nucleus accumbens (NAc). To explore how regulation of CREB in the NAc affects behavior, we used herpes simplex virus (HSV) vectors to elevate CREB expression in this region or to overexpress a dominant-negative mutant CREB (mCREB) that blocks CREB function. Rats treated with HSV-mCREB in place conditioning studies spent more time in environments associated with cocaine, indicating increased cocaine reward. Conversely, rats treated with HSV-CREB spent less time in cocaine-associated environments, indicating increased cocaine aversion. Studies in which drug-environment pairings were varied to coincide with either the early or late effects of cocaine suggest that CREB-associated place aversions reflect increased cocaine withdrawal. Because cocaine withdrawal can be accompanied by symptoms of depression, we examined how altered CREB function in the NAc affects behavior in the forced swim test (FST). Elevated CREB expression increased immobility in the FST, an effect that is opposite to that caused by standard antidepressants and is consistent with a link between CREB and dysphoria. Conversely, overexpression of mCREB decreased immobility, an effect similar to that caused by antidepressants. Moreover, the kappa opioid receptor antagonist nor-Binaltorphimine decreased immobility in HSV-CREB- and HSV-mCREB-treated rats, suggesting that CREB-mediated induction of dynorphin (an endogenous kappa receptor ligand) contributes to immobility behavior in the FST. Exposure to the FST itself dramatically increased CREB function in the NAc. These findings raise the possibility that CREB-mediated transcription within the NAc regulates dysphoric states.
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PMID:Altered responsiveness to cocaine and increased immobility in the forced swim test associated with elevated cAMP response element-binding protein expression in nucleus accumbens. 1154 50


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